Is junk DNA really rubbish?

’Junk DNA’ , which is part of our genome (our DNA), doesn’t give instructions to make a protein like the non-junk bits do. But recently, it’s been shown to have a role in increased breast cancer risk.

It’s a situation we’re all too familiar with. You’re clearing out those dusty cupboards at home, blissfully getting rid of the rubbish, and then someone steps in and says that an item you’ve earmarked for the dustbin is not “junk” and could actually be useful.

It turns out that this sort of debate doesn’t just happen at home, it happens in the world of science too. ’Junk DNA’ , which is part of our genome (our DNA), doesn’t give instructions to make a protein like the non-junk bits do. But recently, it’s been shown to have a role in increased breast cancer risk. So is it really just junk, or does this extra DNA actually suffer from a case of mistaken identity?

A brief genetic history

The concept of inheritance, that biological traits are passed from one generation to the next, originated with the Austrian monk Gregor Mendel in 1866. Mendel was breeding pea plants when he noticed that traits such as flower colour were passed onto offspring. What Mendel had identified were genes – the discrete unit of inheritance – he just didn’t know it. It wasn’t until many years after his death that the significance of his discovery was fully realised.

In the meantime Swiss biochemist Friedrich Miescher was working on a very unglamorous material: pus-soaked bandages collected from a local clinic. Miescher was interested in a new molecule called ‘nuclein’ that he had managed to isolate from the white blood cells found in abundance on these bandages. Miescher’s pus-extracted nuclein was actually DNA – the molecule responsible for carrying the genetic code of life.

But despite these compelling clues, the idea that DNA carried the information needed to pass on traits was initially dismissed as being too simple. Experiments began to show that DNA was made up of just four basic units given the letters A, T, G or C. It seemed much more likely that proteins, which were known to be made up of combinations of 20 differing units called amino acids, were a more suitably complex code for life.

DNA and the molecular biology revolution

It wasn’t until the 1940s and 50s that we found out for sure that DNA was in fact the genetic material that was passed from generation to generation. In 1953, the efforts of James Watson, Francis Crick, Rosalind Franklin and Maurice Wilkins, culminated in the discovery of the chemical structure of DNA. After this the field of molecular biology was born, and it advanced at lightening pace.

In the 1970s scientists began to map out our genetic landscape helped by ‘The Sanger Method’, which made it possible to read the order of letters in a molecule of DNA. This led to an interesting observation. Not all of our DNA was made up of genes. There were bits of our genome which read like gibberish and didn’t seem to have any obvious function. They didn’t make anything, unlike the genes which made proteins. This led to the idea that perhaps not all of our DNA was actually useful.

The term ‘Junk DNA’ started to be used. The 1990s saw the start of the Human Genome Project and, in 2003, it was confirmed that of the 3 billion letters that make up our genetic code, less than 2% provides the information needed to make the proteins needed for life.

So what does the rest do? Surely it can’t all be rubbish?

Breast cancer risk and ‘junk DNA’

In the decade that followed our obsession grew with trying to find genetic ‘markers’ within the DNA code. These were often single letter changes (known as single nucleotide polymorphisms) at a certain location within a person’s genetic code, which may be associated with, and thereby act as a marker for, many chronic and debilitating diseases.

These studies have so far allowed over 70 common single letter changes associated with breast cancer risk to be identified. But what’s been most surprising is that some of these variants, these single letter changes, are found in long stretches of so-called junk DNA known as ‘gene deserts.’ So why would there be an association between single letter variations in junk DNA and increased breast cancer risk? How does it work when the junk-DNA doesn’t actually code for anything?

Non-coding DNA as a regulator?

Research led by our scientist Dr Olivia Fletcher at the Breakthrough Toby Robins Breast Cancer Research Centre has shed some light on this rather intriguing puzzle. In her study, published in Genome Research, Olivia’s team focused on three of these desolate gene deserts and used a novel technique to study the interactions between the ‘junk” DNA’ in gene deserts associated with breast cancer and far off DNA up to millions of letters away in the genome.

They found that making single letter changes in the regions of ‘junk DNA’, caused them to physically interact with genes known to be involved in breast cancer, providing evidence that ‘junk DNA’ may have a part to play in the development of breast cancer.

Talking about her findings, Olivia said: “Our research suggests that some of these single letter changes may be raising the risk of breast cancer by physically interacting with genes in distant parts of the genome, in order to turn their activity up or down”.

“This provides important clues about the causes of breast cancer, as well as shining a light on the roles played by gene deserts – fascinating, gene-less regions of DNA, the mystery of which we are only just beginning to understand.”

So it looks like junk DNA really might be useful after all. Still, we’re not sure about that pile of junk at home…might be time to get down to the charity shop.

About the author

Dr Emma Blamont is a Senior Research Officer at Breast Cancer Now. She has a PhD in Immunology and is outright fanatical about the subject.